Traditionally, in chemical processes, a method of separating a specific ingredient which has been dissolved in liquid as a solid has been widely used. This is because the solidification (crystallization) of only a specific ingredient enables separation and purification after the reaction to be performed readily. This method, for example, in sequential multi-step syntheses such as compound library synthesis or the like used in the recent development and research of drugs, etc. enables the solidified (crystallized) substance to be easily separated and purified by solidifying (crystallizing) a necessary or unnecessary compound after the completion of each reaction. Therefore, complications in the separation and/or purification process which have traditionally caused problems can be resolved.
Furthermore, a method of realizing the separation of a dissolved specific ingredient from other ingredients is also used by selectively dissolving the specific ingredient in a specific phase (selective partition) according to the phase separation of liquid. This method enables a specific ingredient to be separated without solidification (crystallization), thereby contributing to expediting and simplification of the process.
Such a solidification (crystallization) of a specific ingredient dissolved in solution or a selective dissolution of a specific ingredient in a specific phase of liquid (selective partition) can be realized by fulfilling certain conditions with respect to chemical and physical properties of the compound and the relationship with a solvent.
However, the conditions of solidification (crystallization) and selective dissolution (selective partition) must be empirically searched in most cases by trial and error. Especially, in sequential multi-step syntheses, it becomes necessary to examine the conditions of each step based on the specific property of a compound synthesized in each step, thereby having required tremendous amounts of money and time for the process development.
Therefore, there has been proposed a carrier molecule having a linker capable of sensitively perceiving the alteration of a solvent composition so as to reversibly change the soluble state and insoluble (crystallization) state, or selectively dissolving a specific dissolved ingredient into a specific phase in high concentration (selective partition) with the phase separation of the liquid. Such a carrier molecule can bind various compounds via the linker. Therefore, the bound compound can easily change states with the carrier molecule from a soluble state to an insoluble (crystallization) state or vice versa. Alternatively, the compound bound to the carrier molecule can be selectively dissolved in high concentration in a specific phase of liquid separated into multiphase (selective partition).
Furthermore, even when the chemical structure of a compound bound to such a carrier by the sequential multi-step reaction alters, the carrier molecule is capable of reversibly recreating the soluble state and insoluble (crystallized) state or dissolving in a specific phase of liquid separated into multiple phases selectively in high concentration (selective partition) under approximately the same conditions.
Using such a carrier molecule capable of reversibly changing the soluble state and insoluble (crystallized) state or inducing the selective partition state, it is possible to selectively separate an objective compound for separation from a homogeneous solution state while utilizing general knowledge of the liquid phase reaction in organic chemistry. That is, it has become possible to separate a specific compound after the liquid phase reaction while leaving other soluble ingredients in solution.
Concerning a carrier capable of reversibly repeating the soluble state and insoluble state, for example, a method of using a polymer soluble in solvents such as poly(ethylene glycol) is known (see Non-patent Document 1).
Non-patent Document 1: “Liquid-phase combinatorial synthesis” Hyunsoo Han, Mary M. Wolfe, Sydney Brenner, and Kim D. Janda, Proc. Natl. Acad. Sci. USA, Vol. 92, pp. 6419-6423, July 1995 Chemistry.